Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Clin Genet. 2010 Sep;78(3):275-81. doi: 10.1111/j.1399-0004.2010.01384.x. Epub 2010 Feb 11.
Dystroglycanopathies are a heterogeneous group of disorders caused by defects in the glycosylation pathway of alpha-dystroglycan. The clinical spectrum ranges from severe congenital muscular dystrophy with structural brain and eye involvement to a relatively mild adult onset limb-girdle muscular dystrophy without brain abnormalities and normal intelligence. Mutations have been identified in one of six putative or demonstrated glycosyltransferases. Many different FKRP mutations have been identified, which cover the complete clinical spectrum of dystroglycanopathies. In contrast to the other known genes involved in these disorders, genotype-phenotype correlations are not obvious for FKRP mutations. To date, no homozygous or compound heterozygous null mutations have been identified in FKRP, suggesting that null mutations in FKRP could result in embryonic lethality. We report a family with two siblings carrying a homozygous mutation in the start codon of FKRP that is likely to result in a loss of functional FKRP protein. The clinical phenotype of the patients was consistent with Walker-Warburg syndrome, the most severe disorder in the disease spectrum of dystroglycanopathies.
肌营养不良聚糖蛋白病是一组由α- 肌聚糖糖基化途径缺陷引起的异质性疾病。临床表现范围从严重的先天性肌营养不良伴有结构脑和眼异常到相对较轻的成年起病的肢带型肌营养不良，无脑部异常和正常智力。已在六个假定或已证实的糖基转移酶之一中发现突变。已经发现了许多不同的 FKRP 突变，这些突变涵盖了肌营养不良聚糖蛋白病的完整临床谱。与这些疾病中涉及的其他已知基因相比，FKRP 突变的基因型-表型相关性不明显。迄今为止，在 FKRP 中尚未发现纯合或复合杂合的无义突变，这表明 FKRP 中的无义突变可能导致胚胎致死。我们报告了一个家系，其中两个兄弟姐妹携带 FKRP 起始密码子的纯合突变，这很可能导致 FKRP 功能性蛋白的缺失。患者的临床表现与 Walker-Warburg 综合征一致，这是肌营养不良聚糖蛋白病谱中最严重的疾病。
